Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review

BACKGROUND: Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in progressive MS, causing permanent axonal loss and irreversible disabilities. Strategies aimed at enhancing remyelination are critical to attenuate disease progression. OBJECTIVE: We systematically reviewed recent advances in neuroprotective and regenerative therapies for MS, covering preclinical and clinical studies. METHODS: We searched three biomedical databases using defined keywords. Two authors independently reviewed articles for inclusion based on pre-specified criteria. The data were extracted from each study and assessed for risk of bias. RESULTS: Our search identified 7351 studies from 2014 to 2020, of which 221 met the defined criteria. These studies reported 262 interventions, wherein 92% were evaluated in animal models. These interventions comprised protein, RNA, lipid and cellular biologics, small molecules, inorganic compounds, and dietary and physiological interventions. Small molecules were the most highly represented strategy, followed by antibody therapies and stem cell transplantation. CONCLUSION: While significant strides have been made to develop regenerative treatments for MS, the current evidence illustrates a skewed representation of the types of strategies that advance to clinical trials. Further examination is thus required to address current barriers to implementing experimental treatments in clinical settings.